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Role of Disease and Macronutrient Dose in the Randomized Controlled EPaNIC Trial
Open accessAbstract
Rationale: Early parenteral nutrition to supplement insufficient enteral feeding during intensive care (early PN) delays recovery as compared with withholding parenteral nutrition for 1 week (late PN). Objectives: To assess whether deleterious effects of early PN relate to severity of illness or to the dose or type of macronutrients. Methods: Secondary analyses of a randomized controlled trial (EPaNIC; n = 4,640) performed in seven intensive care units from three departments in two Belgian hospitals. In part 1, all patients were included to assess the effect of the randomized allocation to early PN or late PN in subgroups of patients with increasing-on-admission severity of illness. In part 2, observationally, the association of the amount and type of macronutrients with recovery was documented in those patient cohorts still present in intensive care on Days 3, 5, 7, 10, and 14. Measurements and Main Results: The primary end point was time to live discharge from the intensive care unit. For part 1, a secondary end point, acquisition of new infections, was also analyzed. All statistical analyses were performed by univariable and adjusted multivariable methods. In none of the subgroups defined by type or severity of illness was a beneficial effect of early PN observed. The lowest dose of macronutrients was associated with the fastest recovery and any higher dose, administered parenterally or enterally, was associated with progressively more delayed recovery. The amount of proteins/amino acids rather than of glucose appeared to explain delayed recovery with early feeding. Conclusions: Early combined parenteral/enteral nutrition delayed recovery irrespective of severity of critical illness. No dose or type of macronutrient was found to be associated with improved outcome. Clinical trial registered with www.clinicaltrials.gov (NCT00512122).
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“Higher protein intakes during the acute phase might be linked to greater muscle wasting and ICU-acquired weakness.1,15”
From Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3). (2023) · cites this paper as [15]
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“A post hoc analysis of this trial suggested that the highest amount of nutritional intake was associated with a higher infection rate and a delay in recovery [37].”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [37]
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“In addition, the post hoc analysis of EPaNIC (173, 174) studies suggested that early administration of amino acids (mainly at day 3) was associated with a later live discharge from the ICU, questioning the indication of administrating amino acids in the early stay in the ICU (175).”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [174]
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Cites
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Self-citationTaylor, B. E., McClave, S. A., Martindale, R. G., Warren, M. M., Johnson, D. R., Braunschweig, C., McCarthy, M. S., Davanos, E., Rice, T. W., Cresci, G. A., et al. (2016) · Critical Care Medicine · doi:10.1097/ccm.0000000000001525 · Cited by 1,476
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ESPEN guideline on clinical nutrition in the intensive care unit.
Singer, P., Blaser, A. R., Berger, M. M., Alhazzani, W., Calder, P. C., Casaer, M. P., Hiesmayr, M., Mayer, K., Montejo, J. C., Pichard, C., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.08.037 · Cited by 2,904
Self-citationVanhorebeek, I., Latronico, N., & den Berghe, G. V. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-05944-4 · Cited by 840
Trial of the Route of Early Nutritional Support in Critically Ill Adults
Harvey, S. E., Parrott, F., Harrison, D. A., Bear, D. E., Segaran, E., Beale, R., Bellingan, G., Leonard, R., Mythen, M. G., & Rowan, K. M. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409860 · Cited by 618
Post‐intensive care syndrome: its pathophysiology, prevention, and future directions
Inoue, S., Hatakeyama, J., Kondo, Y., Hifumi, T., Sakuramoto, H., Kawasaki, T., Taito, S., Nakamura, K., Unoki, T., Kawai, Y., et al. (2019) · Acute Medicine & Surgery · doi:10.1002/ams2.415 · Cited by 653
Metabolic and nutritional support of critically ill patients: consensus and controversies
Preiser, J.-C., van Zanten, A. R., Berger, M. M., Biolo, G., Casaer, M. P., Doig, G. S., Griffiths, R. D., Heyland, D. K., Hiesmayr, M., Iapichino, G., et al. (2015) · Critical Care · doi:10.1186/s13054-015-0737-8 · Cited by 416
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Metadata
- Authors
- Casaer, M. P., Wilmer, A., Hermans, G., Wouters, P. J., Mesotten, D., & Van den Berghe, G.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- KU Leuven (BE)
- Laboratory and Department of Intensive Care Medicine and
- Corresponding author
- Casaer, Michael P.
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-02-01
- Volume
- 187
- Issue
- 3
- Pages
- 247-255
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W1840057839
- Semantic Scholar
- 37a3fd62d1564a467a4fe20b913801329a33e0e8
- Cited by
- 307
- References
- 46
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 26 · 2023: 22 · 2022: 24 · 2021: 28 · 2020: 18 · 2019: 23 · 2018: 33 · 2017: 27 · 2016: 12 · 2015: 27 · 2014: 23 · 2013: 9
- FWCI
- 17.54
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Funders
- European Commission
- Vlaamse regering
- FP7 Ideas: European Research Council (321670)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Health Sciences › Medicine › Surgery › Enhanced Recovery After Surgery
- Keywords
- early parenteral nutrition, critical illness, glucose supplementation, enteral nutrition, intensive care unit discharge, infection acquisition, disease severity
- MeSH terms
- Aged, Belgium, Energy Intake, Critical Care, Cross Infection, Dietary Carbohydrates, Dietary Proteins, Enteral Nutrition, Female, Humans, Intensive Care Units, Length of Stay, Lipids, Male, Middle Aged, Parenteral Nutrition, Severity of Illness Index, Time Factors, Cohort Studies, Causality, Odds Ratio, Critical Illness, Dietary Supplements, Kaplan-Meier Estimate
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